Generation of CD4+CD45RA+ Effector T Cells by Stimulation in the Presence of Cyclic Adenosine 5′-Monophosphate- Elevating Agents

Abstract

After TCR cross-linking, naive CD4+CD45RA+ T cells switch to the expression of the CD45RO isoform and acquire effector functions. In this study we have shown that cAMP-elevating agents added to anti-CD3- and anti-CD28-stimulated cultures of T lymphocytes prevent acquisition of the CD45RO+ phenotype and lead to the generation of a new subpopulation of primed CD4+CD45RA+ effector cells (cAMP-primed CD45RA). These cells displayed a low apoptotic index, as the presence of dibutyryl cAMP (dbcAMP)-rescued cells from CD3/CD28 induced apoptosis. Inhibition of CD45 splicing by dbcAMP was not reverted by addition of exogenous IL-2. cAMP-primed CD45RA cells had a phenotype characteristic of memory/effector T lymphocytes, as they showed an up-regulated expression of CD2, CD44, and CD11a molecules, while the levels of CD62L Ag were down-regulated. These cells also expressed the activation markers CD30, CD71, and HLA class II Ags at an even higher level than CD3/CD28-stimulated cells in the absence of dbcAMP. In agreement with this finding, cAMP-primed CD45RA cells were very efficient in triggering allogenic responses in a MLR. In addition, cAMP-primed CD45RA cells produce considerable amounts of the Th2 cytokines, IL-4, IL-10, and IL-13, whereas the production of IFN-γ and TNF-α was nearly undetectable. The elevated production of IL-13 by neonatal and adult cAMP-primed CD45RA cells was specially noticeable. The cAMP-dependent inhibition of CD45 splicing was not caused by the production of immunosuppressor cytokines. These results suggest that within the pool of CD4+CD45RA+ cells there is a subpopulation of effector lymphocytes generated by activation in the presence of cAMP-elevating agents.

Phosphodiesterase 7A-Deficient Mice Have Functional T Cells

“…The association of PDE4D to ␤2-adrenergic receptors resulted in desensitization of the receptors. One can speculate that PDE7A may play an important role in the development of memory T cells (35) or the regulation of activation-induced apoptosis in T lymphocytes (36) since it has been shown that cAMP is involved in these aspects of T cell function.…”

CD3+CD4low and CD3+CD8low are induced by HLA-G: novel human peripheral blood suppressor T-cell subsets involved in transplant acceptance

“…Incidentally, soluble CD4 and CD8 coreceptors are believed to be potent inhibitors of T-cell activation by competing with membraneanchored coreceptors, thus preventing T-cell activation via coreceptor/CD3-TCR complex-peptide/MHC interaction. 34 Better graft acceptance was observed in LT and LKT patient groups that all received a liver allograft. Therefore, HLA-G can be considered as a graft acceptance-associated marker whose expression may be up-regulated by liver factors.…”

“…It has been shown that primed CD4 ϩ T cells expressing CD45RA secreted high amounts of IL-4, IL-10, and IL-13, whereas the production of IFN-␥ was very low. 34 This pattern of cytokine production is akin to lymphocytes with a Th2 phenotype. HLA-DR ϩ cells were also overrepresented in the HLA-G-driven CD3 ϩ CD4 low and CD3 ϩ CD8 low T cells compared with CD4 high and CD8 high T cells.…”

Regulatory mechanisms of acetylcholine synthesis and release by T cells

“…Intracellular cAMP is also known as an important physiological mediator of inflammation and a key regulator of immune responses (Suárez et al, 2002).…”